The purpose is to pursue investigations to elucidate and evaluute factors affecting the behavior of peroxisomes (microbodies) under normal and pathological conditons, in an attempt to understand the biological significance of these cytoplasmic organelles. These studies will be performed utilizing the peroxisome proliferative property of certain hypolipidemic compounds referred to as peroxisome proliferators, which include clofibrate, nafenopin, methyl clofenapate, tibric acid, Wy-14643 and SaH 42-348. Morphological and biochemical changes in liver associated with drug induced peroxisome proliferation and the factors which modify these changes will be delineated. Effect of lifetime exposure to selected peroxisome proliferators in rats and mice will be investigated in view of the development of hepatocellular carcinoma in mice chronically treated with nafenopin in our preliminary studies. Freeze-fracture technique will be applied to characterize the structural organization of peroxisome membrane in different cell types. The information obtained from these studies should further our knowledge of peroxisomes.